Findings in the first 4 Strong Heart Study (SHS) exams (high rates of diabetes [DM] and cardiovascular [CV] events and heritability of arterial cardiac phenotypes [LOD=5.3 for left ventricular (LV) mass index on chromosome 12p]) identify SHS participants as being of unusual importance in understanding CV disease biology. Carotid exams in participants in SHS Phase IV showed substantial progression of atherosclerosis over 4 years and showed heritability of arterial size and stiffness. Phase IV echo's showed near doubling of 'LV hypertrophy and decline in LV function over 8 years from Phase II. Initial 1710 months follow-up showed CV events were predicted strongly by discrete carotid plaque but only weakly by intimal-medial thickness (IMT).In SHS Phase V, 3,060 members >15 years old in 3-generation families will be evaluated by carotid and popliteal ultrasound, computerized ECG and echo measures of LV geometry and function. The characteristics of the SHS population and strengths of the investigative groups lead us to focus this renewal to: 1) establish genetic linkage of carotid artery IMT and discrete plaques; 2) assess linkage of LV mass, geometry and newer measures of LV function; 3) examine heritability of ECG measures of cardiac conduction, voltage and repolarization; 4) assess heritability and linkage of popliteal artery IMT and discrete plaque as measures of peripheral arterial disease; 5) assess the separate and joint effects of DM, overweight and hypertension on development of LV hypertrophy and dysfunction over 4 years from the 4thSHS exam; 6) determine the impacts of DM, overweight and hypertension on progression of carotid IMT and discrete plaques since the 4th SHS exam; 7) relate change in ECG measures of LV hypertrophy Andre polarization to changes in echo LV mass and arterial structure and function; 8) assess the prognostic significance of arterial measures made during the 3rd SHS exam and extend analyses of prognostic significance of previously-measured echo and ECG variables; 9) evaluate changes of arterial structure and function in SHS pilot Family Study participants over 8 years and of echo findings over 12 years in cohort members in the SHS Family Study; 10) examine relations of popliteal artery IMT and discrete a thermos to prevalent overt and sub clinical peripheral arterial disease and CV risk factors and 11) evaluate relations of changes in ECG measures of LV hypertrophy, repolarization and ischemia to morbid and mortal events. (End of Abstract)